PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas
| Autor: | Daniela C C, Santos, Peter G, Zaphiropoulos, Cyro F, Neto, Eugênio R A, Pimentel, José A, Sanches, Itamar R G, Ruiz |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Aged 80 and over Male Patched Receptors Skin Neoplasms Base Sequence Molecular Sequence Data Loss of Heterozygosity Basal Cell Nevus Syndrome Receptors Cell Surface Exons Middle Aged Patched-2 Receptor Genomic Instability Gene Expression Regulation Neoplastic Patched-1 Receptor Carcinoma Basal Cell Humans Point Mutation Female Amino Acid Sequence Aged Microsatellite Repeats |
| Zdroj: | International journal of dermatology. 50(7) |
| ISSN: | 1365-4632 |
| Popis: | Basal cell carcinomas (BCCs) are the most frequent human cancer that results from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2.To search for mutations and genomic instability in sporadic and inherited BCCs.DNA obtained from leukocytes and tumor cells was amplified by polymerase chain reaction regarding five exons of PTCH1 and PTCH2 and neighboring microsatellites. Exons were sequenced and compared with the GenBank database.Only D9S180, of six microsatellites, showed loss of heterozygosity in three BCCs (two sporadic and one inherited). One sporadic BCC presented the mutation g.2885GC in exon 17 of PTCH1, which predicts the substitution p.R962T in an external domain of the protein. In addition, the leukocytes and tumor cells of one patient with Gorlin syndrome showed the mutation g.2839TG in the same exon and gene, which predicts a p.E947stop and truncated protein. All control and tumor samples presented IVS9 + 217T in intron 9 of PTCH1.Mutations found in the PTCH1 gene and neighboring repetitive sequences may have contributed to the development of the studied BCCs. |
| Databáze: | OpenAIRE |
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